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Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia.
[aromatase deficiency]
Aromatase
inhibitors
have
been
increasingly
used
in
boys
with
growth
retardation
to
prolong
the
duration
of
growth
and
increase
final
height
.
Multiple
important
roles
of
oestrogen
in
males
point
to
potential
adverse
effects
of
this
strategy
.
Although
the
deleterious
effects
of
aromatase
deficiency
in
early
childhood
and
adulthood
are
well
documented
,
there
is
limited
information
about
the
potential
long
-term
adverse
effects
of
peripubertal
aromatase
inhibition
.
To
address
this
issue
,
we
evaluated
short
-term
and
long
-term
effects
of
peripubertal
aromatase
inhibition
in
an
animal
model
.
Peripubertal
male
Wistar
rats
were
treated
with
aromatase
inhibitor
letrozole
or
placebo
and
followed
until
adulthood
.
Letrozole
treatment
caused
sustained
reduction
in
bone
strength
and
alteration
in
skeletal
geometry
,
lowering
of
IGF
1
levels
,
inhibition
of
growth
resulting
in
significantly
lower
weight
and
length
of
treated
animals
and
development
of
focal
prostatic
hyperplasia
.
Our
observation
of
adverse
long
-term
effects
after
peripubertal
male
rats
were
exposed
to
aromatase
inhibitors
highlights
the
need
for
further
characterisation
of
long
-term
adverse
effects
of
aromatase
inhibitors
in
peripubertal
boys
before
further
widespread
use
is
accepted
.
Furthermore
,
this
suggests
the
need
to
develop
more
selective
oestrogen
inhibition
strategies
in
order
to
inhibit
oestrogen
action
on
the
growth
plate
,
while
beneficial
effects
in
other
tissues
are
preserved
.
